Comparative Analysis of Risk Factors in Declined Kidneys from Donation after Brain Death and Circulatory Death.

Background and objectives: Kidneys from donation after circulatory death (DCD) are more likely to be declined for transplantation compared with kidneys from donation after brain death (DBD). The aim of this study was to evaluate characteristics in the biopsies of human DCD and DBD kidneys that were declined for transplantation in order to rescue more DCD kidneys. Materials and Methods: Sixty kidney donors (DCD = 36, DBD = 24) were recruited into the study and assessed using donor demographics. Kidney biopsies taken post cold storage were also evaluated for histological damage, inflammation (myeloperoxidase, MPO), von Willebrand factor (vWF) expression, complement 4d (C4d) deposition and complement 3 (C3) activation using H&E and immunohistochemistry staining, and Western blotting. Results: More DBD donors (16/24) had a history of hypertension compared with DCDs (8/36, p = 0.001). The mean warm ischemic time in the DCD kidneys was 12.9 ± 3.9 min. The mean cold ischemic time was not significantly different between the two groups of kidney donors (DBD 33.3 ± 16.7 vs. DCD 28.6 ± 14.1 h, p > 0.05). The score of histological damage and MPO, as well as the reactivity of vWF, C4d and C3, varied between kidneys, but there was no significant difference between the two donor types (p > 0.05). However, vWF reactivity might be an early indicator for loss of tissue integrity, while C4d deposition and activated C3 might be better predictors for histological damage. Conclusions: Similar characteristics of DCD were shown in comparison with DBD kidneys. Importantly, the additional warm ischemic time in DCD appeared to have no further detectable adverse effects on tissue injury, inflammation and complement activation. vWF, C4d and C3 might be potential biomarkers facilitating the evaluation of donor kidneys

Magnetic characterization of superparamagnetic nanoparticles pulled through model membranes

BACKGROUND: To quantitatively compare in-vitro and in vivo membrane transport studies of targeted delivery, one needs characterization of the magnetically-induced mobility of superparamagnetic iron oxide nanoparticles (SPION). Flux densities, gradients, and nanoparticle properties were measured in order to quantify the magnetic force on the SPION in both an artificial cochlear round window membrane (RWM) model and the guinea pig RWM. METHODS: Three-dimensional maps were created for flux density and magnetic gradient produced by a 24-well casing of 4.1 kilo-Gauss neodymium-iron-boron (NdFeB) disc magnets. The casing was used to pull SPION through a three-layer cell culture RWM model. Similar maps were created for a 4 inch (10.16 cm) cube 48 MGOe NdFeB magnet used to pull polymeric-nanoparticles through the RWM of anesthetized guinea pigs. Other parameters needed to compute magnetic force were nanoparticle and polymer properties, including average radius, density, magnetic susceptibility, and volume fraction of magnetite. RESULTS: A minimum force of 5.04 × 10(-16 )N was determined to adequately pull nanoparticles through the in-vitro model. For the guinea pig RWM, the magnetic force on the polymeric nanoparticles was 9.69 × 10(-20 )N. Electron microscopy confirmed the movement of the particles through both RWM models. CONCLUSION: As prospective carriers of therapeutic substances, polymers containing superparamagnetic iron oxide nanoparticles were succesfully pulled through the live RWM. The force required to achieve in vivo transport was significantly lower than that required to pull nanoparticles through the in-vitro RWM model. Indeed very little force was required to accomplish measurable delivery of polymeric-SPION composite nanoparticles across the RWM, suggesting that therapeutic delivery to the inner ear by SPION is feasible

Advance care planning uptake among patients with severe lung disease: A randomised patient preference trial of a nurse-led, facilitated advance care planning intervention

Objective Advance care planning (ACP) clarifies goals for future care if a patient becomes unable to communicate their own preferences. However, ACP uptake is low, with discussions often occurring late. This study assessed whether a systematic nurse-led ACP intervention increases ACP in patients with advanced respiratory disease. Design A multicentre open-label randomised controlled trial with preference arm. Setting Metropolitan teaching hospital and a rural healthcare network. Participants 149 participants with respiratory malignancy, chronic obstructive pulmonary disease or interstitial lung disease. Intervention Nurse facilitators offered facilitated ACP discussions, prompted further discussions with doctors and loved ones, and assisted participants to appoint a substitute medical decision-maker (SDM) and complete an advance directive (AD). Outcome measures The primary measure was formal (AD or SDM) or informal (discussion with doctor) ACP uptake assessed by self-report (6 months) and medical notes audit. Secondary measures were the factors predicting baseline readiness to undertake ACP, and factors predicting postintervention ACP uptake in the intervention arm. Results At 6 months, formal ACP uptake was significantly higher (p<0.001) in the intervention arm (54/106, 51%), compared with usual care (6/43, 14%). ACP discussions with doctors were also significantly higher (p<0.005) in the intervention arm (76/106, 72%) compared with usual care (20/43, 47%). Those with a strong preference for the intervention were more likely to complete formal ACP documents than those randomly allocated. Increased symptom burden and preference for the intervention predicted later ACP uptake. Social support was positively associated with ACP discussion with loved ones, but negatively associated with discussion with doctors. Conclusions Nurse-led facilitated ACP is acceptable to patients with advanced respiratory disease and effective in increasing ACP discussions and completion of formal documents. Awareness of symptom burden, readiness to engage in ACP and relevant psychosocial factors may facilitate effective tailoring of ACP interventions and achieve greater uptake. Trial registration number ACTRN12614000255684. © Published by the BMJ Publishing Group Limite

Dynamics and Topological Aspects of a Reconstructed Two-Dimensional Foam Time Series Using Potts Model on a Pinned Lattice

We discuss a method to reconstruct an approximate two-dimensional foam structure from an incomplete image using the extended Potts mode with a pinned lattice we introduced in a previous paper. The initial information consists of the positions of the vertices only. We locate the centers of the bubbles using the Euclidean distance-map construction and assign at each vertex position a continuous pinning field with a potential falling off as $1/r$. We nucleate a bubble at each center using the extended Potts model and let the structure evolve under the constraint of scaled target areas until the bubbles contact each other. The target area constraint and pinning centers prevent further coarsening. We then turn the area constraint off and let the edges relax to a minimum energy configuration. The result is a reconstructed structure very close to the simulation. We repeated this procedure for various stages of the coarsening of the same simulated foam and investigated the simulation and reconstruction dynamics, topology and area distribution, finding that they agree to good accuracy.Comment: 31 pages, 20 Postscript figures Accepted in the Journal of Computational Physic

Intra-amniotic delivery of CFTR-expressing adenovirus does not reverse cystic fibrosis phenotype in inbred CFTR-knockout mice

This article is available open access through the publisher’s website at the link below. Copyright © 2008 The American Society of Gene Therapy.Due to its early onset and severe prognosis, cystic fibrosis (CF) has been suggested as a candidate disease for in utero gene therapy. In 1997, a study was published claiming that to how transient prenatal expression of CF transmembrane conductance regulator (CFTR) from an in utero –injected adenovirus vector could achieve permanent reversal of the CF intestinal pathology in adult CF knockout mice, despite the loss of CFTR transgene expression by birth. This would imply that the underlying cause of CF is a prenatal defect for which lifelong cure can be achieved by transient prenatal expression of CFTR. Despite criticism at the time of publication, no independent verification of this contentious finding has been published so far. This is vital for the development of future therapeutic strategies as it may determine whether CF gene therapy should be performed prenatally or postnatally. We therefore reinvestigated this finding with an identical adenoviral vector and a knockout CF mouse line (CftrtmlCam) with a completely inbred genetic background to eliminate any effects due to genetic variation. After delivery of the CFTR-expressing adenovirus to the fetal mouse, both vector DNA and transgenic CFTR expression were detected in treated animals postpartum but statistically no significant difference in survival was observed between the Cftr–/– mice treated with the CFTR-adenovirus and those treated with the control vector.Sport Aiding Medical Research for Kids, the Cystic Fibrosis Trust, and the Katharine Dormandy Trust

Randomized trial evaluating the framing of cardiovascular risk and its impact on blood pressure control [ISRCTN87597585]

BACKGROUND: The format or frame in which the results of randomized trials are presented has been shown to influence health professional's self-reported practice. We sought to investigate the effect of framing cardiovascular risk as two different formats in a randomized trial. METHODS: We recruited 457 patients aged between 60 and 79 years with high blood pressure from 20 family practices in Avon, UK. Patients were randomized to cardiovascular risk presented either as 1) an absolute risk level (AR) or as 2) the number needed to treat to prevent an adverse event (NNT). The main outcome measures were: 1) percentage of patients in each group with a five-year cardiovascular risk ≥ 10%, 2) systolic and diastolic blood pressure, 3) intensity of prescribing of cardiovascular medication. RESULTS: Presenting cardiovascular risk as either an AR or NNT had no impact reducing cardiovascular risk at 12 month follow up, adjusted odds ratio 1.53 (95%CI 0.76 to 3.08). There was no difference between the two groups in systolic (adjusted difference 0.97 mmHg, 95%CI -2.34 mmHg to 4.29 mmHg) or diastolic (adjusted difference 0.70 mmHg, 95%CI -1.05 mmHg to 2.45 mmHg) blood pressure. Intensity of prescribing of blood pressure lowering drugs was not significantly different between the two groups at six months follow up. CONCLUSIONS: Presenting cardiovascular risk in clinical practice guidelines as either an AR or NNT had a similar influence on patient outcome and prescribing intensity. There is no difference in patient outcomes when these alternative formats of risk are used in clinical practice guidelines

Interaction of Copper-Amine With Southern Pine: Retention and Migration

The retention and leachability of copper in copper-amine (Cu-EA)-treated southern pine (SP) are influenced by the formulation and the composition of copper-amine treating solutions. The sources of copper used, Cu(OH)2, CuCO3, CuSO4, and Cu(NO3)2, in the copper-amine complex formulation affect the leachability of copper. Data show that copper-amine from CuSO4- and Cu(NO3)2-treated wood has less copper loss during laboratory water leaching than that from Cu(OH)2- and CuCO3-treated wood. Increasing the amine-to-copper molar ratio increases the copper retention by wood, but reduces the leach resistance of copper. The nature of amine ligands, such as monoethanolamine (primary amine), 2-methylamino-ethanol (secondary amine), and N, N-dimethyl-ethanolamine (tertiary amine), has some effect on copper retention and copper leaching. As the molecular weight of amine ligands increases, copper loss during leaching decreases

Suicide in cancer patients in South East England from 1996 to 2005: a population-based study

BACKGROUND: Studies from around the world have shown that suicide risk is increased in cancer patients, but no previous detailed analysis has been carried out in England